Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Utility of drug response modulators to increase therapeutic:toxic ratio of anticancer drugs in the treatment of refractory malignancies is becoming desirable. In this study, we have attempted to potentiate the tumor cell killing ability of Adriamycin (ADR) against chronic myeloid leukemia cells (CML), in the presence of vitamin K3. Cell growth was evaluated by the MTT assay and the 3H-thymidine incorporation inhibition assay. A highly significant (p less than 0.001) inhibition of cell survival and 3H-thymidine incorporation was effected in CML cells exposed to the combination of ADR and vitamin K3. When the CML cells were treated with ADR and vitamin K3 simultaneously, a greater fragmentation of the intact DNA was revealed as observed by the enhanced formation of DNA single strand breaks. Results demonstrate the therapeutic significance of employing vitamin K3 as an adjuvant in CML chemotherapy with ADR.
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PMID:Single and combination treatment with vitamin K3 and adriamycin: in vitro effects on cell survival and DNA damage in human chronic myeloid leukemia cells. 177 Dec 99

Platelet functions and morphological changes of megakaryocytes were investigated in three cases with chronic neutrophilic leukemia (CNL). The bleeding time was prolonged, the ADP, collagen, epinephrine-induced aggregation of platelets decreased in one case. The adhesiveness, epinephrine-induced aggregation and adenine nucleotide content of platelets decreased in one other case. Megakaryocyte size in CNL was larger than in CML and this difference of the megakaryocyte sizes was related to DNA content distribution of the megakaryocytes. Atypical megakaryocytes were apparently found in one case. The present study suggests that CNL is a stem cell disorder.
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PMID:[Changes in the megakaryocyte-platelet system in chronic neutrophilic leukemia]. 177 59

In vitro amplification of genomic or cDNA sequences by polymerase chain reaction (PCR) is one of the most powerful tools in recent molecular biology. More than 10(5) copies of DNA sequence ranging from 50 bp to 7 kb can be synthesized in a couple of hours. Ever since its development, PCR has attracted much attention because this strategy would allow the detection of minimal residual disease (MRD) at a very low level. The first successful application of this ultra-sensitive technique was the detection of residual tumor cells carrying a 14;18 translocation in follicular lymphoma. The abnormal transcripts caused by 9;22 translocation in chronic myelocytic leukemia (CML) was also exploited for the amplification to detect the MRD. These techniques have successfully shown the detection of one leukemic cell in 100,000 normal cells. Besides leukemic specific sequences caused by chromosome and gene translocations, unique sequences caused by rearrangements in IgH or TCR gamma, delta chain genes have been used as clonal markers for tumor cells. By targetting these sequences for PCR amplification, almost all ALL patients can be analyzed for MRD. The successive measurement of MRD might contribute to improvement of treatments for leukemic patients.
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PMID:[The detection of minimal residual disease in leukemia by in vitro DNA amplification]. 177 67

The prognostic value of three DNA cytometric parameters--stemline ploidy (STL), stemline shoulder fraction (SSF) and "proliferative" fraction (PRF)--for the prediction of disease transformation and survival was examined for 20 patients with chronic myelogenous leukemia (CML) during the course of their disease and compared with two commonly used hematologic parameters (degree of leukocytosis and percentage of circulating leukemic progenitor cells). With disease progression, STL and SSF increased significantly, whereas PRF showed a steady decrease from diagnosis to blast crisis. The most significant part of these changes took place during the chronic phase, before the clinical onset of disease transformation. Hematologic parameters, in comparison, revealed significant changes later, shortly before blast crisis. The remaining duration of the chronic phase diminished from 25.5 months at the time of diagnosis, when the median STL was 2.0c, to 19.6 months for patients showing an STL of 2.1c, to 15.0 months with an STL of 2.2c and to 1.0 months for those with an STL of greater than or equal to 2.3c. Prognostically relevant limits for SSF and PRF were at 20%. When the SSF passed this limit or the PRF fell below it, the mean remaining chronic phase of these patients amounted to only 14.1 and 10.1 months. Interactive cytometry allows analysis of the DNA cytometric equivalent of changes in leukemic progenitor cells, which are well known from cytogenetic and cell kinetic studies. These three DNA cytometric parameters reflect the "natural history" of CML with the development of a cytogenetically hyperdiploid clone during disease progression in most patients and a simultaneous loss of proliferative potential on the level of myelobasts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monitoring DNA cytometric parameters during the course of chronic myelogenous leukemia. 180 86

Cancer is caused by specific DNA damage. Several common mechanisms that cause DNA damage result in specific malignant disorders: First, proto-oncogenes can be activated by translocations. For example, translocation of the c-myc proto-oncogene from chromosome 8 to one of the immunoglobulin loci on chromosomes 2, 14, or 22 results in Burkitt's lymphomas. Translocation of the c-abl proto-oncogene from chromosome 9 to the BCR gene located on chromosome 22 produces a hybrid BCR/ABL protein resulting in chronic myelogenous leukemia. Second, proto-oncogenes can be activated by point mutations. For example, point mutations of genes coding for guanosine triphosphate-binding proteins, such as H-, K-, or N-ras or G proteins, can be oncogenic as noted in a large variety of malignant neoplasms. Proteins from these mutated genes are constitutively active rather than being faithful second messengers of periodic extracellular signals. Third, mutations that inactivate a gene can result in tumors if the product of the gene normally constrains cellular proliferation. Functional loss of these "tumor suppressor genes" is found in many tumors such as colon and lung cancers. The diagnosis, classification, and treatment of cancers will be greatly enhanced by understanding their abnormalities at the molecular level.
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PMID:Molecular mechanisms of cancer. 181 12

Recently, Molecular genetics has remarkably advanced and it is introduced in medicine. The use of recombinant DNA methods for the diagnosis of leukemias is reported with special reference to the contribution of cytogenetic findings, such as specific chromosome aberrations previously obtained. Therefore, cytogenetic studies on Ph1 chromosome and other specific aberrations found in leukemias are historically reviewed. Using Southern blotting, PFGE, PCR, and in situ chromosome mapping techniques we have analyzed many cases with CML and cases with ALL. We found M-bcr rearrangements not only in standard Ph1, but also in complex types and in Ph1 (-) ve CML. Chromosomal in situ hybridization was very informative identifying transposition of bcr and abl genes between chromosomes 22 and 9. In this connection, FISH (fluorescence in situ hybridization) technique was developed by us, which is expected to have an exceptional power of analysis. ALL had either M-bcr or m-bcr rearrangements, the latter being identified by PFGE. Next, application of PCR technique that enables to obtain more than 10(5) copies of target sequences could monitor minimal residual diseases in CML. Recently, the relevant gene were cloned respectively in FAB-M2 and APL (FAB-M3), so that detection of minimal residual diseases will be successfully performed in these types of leukemia. Finally, targeting chemotherapy using antisense sequences is prospectively described.
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PMID:[Advances in molecular genetic diagnosis of leukemia]. 181 42

The configuration of the P53 tumor suppressor gene was investigated in 43 Chinese patients with chronic myelogenous leukemia (CML), 32 in chronic phase and 11 in blastic crisis. No obvious rearranged DNA band was detected in Southern blot patterns from patients at both stages of the disease. However, P53 gene deletion events were observed in 4 out of 11 cases in blast crisis. This finding was associated with a cytogenetically identifiable chromosome 17p deletion, iso(17q), in only one out of 4 cases.
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PMID:Monoallelic deletions of the P53 gene in Chinese patients with chronic myelogenous leukemia in blastic crisis. 181 2

Methylation of some genes is associated with tumoral progression in numerous cancers. The short arm of chromosome 11 is a hot spot for such methylations. The calcitonin gene (11p15) seems to be a good marker of these phenomenons, particularly in acute leukemias. The abnormal methylation pattern of the calcitonin gene in leukemic cells is visualized by Southern blotting after digestion of tumoral DNA with isoschizomeric restriction enzymes which are methylation sensitive or not. These studies seem of interest for acute myeloblastic leukemias (AML) where few molecular markers are available. Moreover hypermethylation of the calcitonin gene correlates with acceleration and transformation of chronic myeloid leukemia (CML). Sequential studies are warranted to evaluate if such techniques might help, especially for timing of bone marrow transplantation in CML.
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PMID:Hypermethylation of the calcitonin gene and leukemia. 181 14

A 20-year old patient is presented with generalized lymphadenopathy, splenomegaly, hyperleukocytosis and a bone marrow biopsy showing panmyelosis with predominance of immature granulocytes. Lymph node biopsy showed a histopathological feature that was diagnosed as a chronic granulocytic leukemia in blast crisis. The cell surface phenotype of these blast cells showed predominance of immature CD1+, CD7+ T lymphocytes. The T cell lineage was confirmed by DNA rearrangement studies. In addition, the patient showed erythrocytosis, arterial O2 saturation of 92% and thrombocytosis, characteristics of polycythemia vera. After chemotherapy, the patient relapsed with similar symptoms and lymph node cells of similar immature T phenotype. With a revised diagnosis of immature T cell lymphoma associated to a myeloproliferative disorder and polyglobulia, the patient received a combined treatment of Cyclophosphamide-Adriamycin-Vincristine-VM26-Prednisone. Two months later, the patient relapsed again. He received the first phase of induction of the BFM protocol, with partial clinical remission. Five months later, the patient returned with fever, polyadenopathy and splenomegaly. Lymph node cells showed again immature T cell phenotype. The patient was next treated with the m-BACOD scheme, with no response and progression of the disease and he died few days later due to massive bleeding and cardiorespiratory failure.
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PMID:[T lymphoma of immature phenotype associated with polycythemia vera]. 182 May 2

Seventy five radiation-related leukemia patients in Hiroshima including 16 patients exposed to more than one Gray were cytogenetically examined. Statistical analysis of data on the frequencies of chromosomal aberrations in the survivor groups according to bone marrow doses by DS86 estimation revealed that the heavily exposed group tended to have significantly higher aberration rates compared to the non-exposed group. Furthermore, the chromosomal aberrations in the survivors were observed to be of a more complex nature and had the characteristic findings of secondary leukemia. These observations therefore suggest that patients with a history of heavy exposure to atomic bomb radiation had leukemic cells originating from a stem cell which had been damaged by irradiation at the time of the bombing as well as cells involved in complex chromosome abnormalities. Molecular biologic studies on ras genes in acute and chronic leukemias and the bcr gene in chronic myelocytic leukemia were performed in exposed and non-exposed groups. So far, no distinctive differences have been observed in the frequency and sites of point mutations in N- and K-ras genes or in the rearrangement of the bcr gene. Further, retrospective analysis using DNA from leukemia patients who developed this disease in the early period from atomic bomb radiation exposure would be useful for the elucidation of the mechanisms of radiation-induced leukemia.
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PMID:Cytogenetic and molecular changes in leukemia among atomic bomb survivors. 182 62


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